Acne is a skin disease that often scars those afflicted, and can afflict patients at young ages--typically teen years--when their self-images are the most sensitive. The scarring is commonly permanent even if the condition is treated with medications. Some patients experience symptoms well into their adult years.
Acne is believed to be caused typically when the sebaceous glands become clogged due to skin cell debris and an excess of a specific type of skin bacteria. Sebaceous glands are located within the dermis layer of the skin along the hair shaft. Keratin and other chemicals associated with the skin can clog the hair shaft and the sebaceous gland. The bacteria, Propionibacterium acnes (P. acnes), which is always present, multiplies to a much greater degree when the sebaceous glands are clogged because the bacteria prefer an anaerobic environment, which is present when the glands become clogged.
P. acnes produces a lipase enzyme that hydrolyzes triglycerides of the sebaceous gland into free fatty acids. The fatty acids along with bacterial proteins and keratin can irritate the skin tissues. This may lead to an inflammatory response and the formation of an acne lesion.
Although the exact cause of acne is unknown, hormones, genetics, and environmental factors all seem to play a role. Androgens, such as testosterone, play an important role in the development of acne lesions. This is evidenced by the correlation between the onset of puberty and the development of acne, and the fact that acne is generally more severe in males than in females.
The type of acne treatments currently recommended depend on the type and the severity of the acne. A few over-the-counter medications (e.g., benzoyl peroxide and salicylic acid) can be used for mild forms of acne, but are ineffective for the moderate and severe cases of acne.
Tretinoin (Retin-A) is often used in combination with or as a replacement for treatment with benzoyl peroxide. Tretinoin is a derivative of vitamin A and is available for topical use. It acts to prevent comedone formation through its antikeratinization effect. The side effects of tretinoin include heightened sensitivity to exposure to sunlight and local irritation.
Topical antibiotics are sometimes used for treatment of patients with mild to moderate inflammatory acne, but are ineffective against more severe inflammatory acne. To the extent antibiotics have effects against more severe (i.e. inflammatory) forms of acne, the antibiotics must be systemically administered, usually at high doses (e.g., 500 to 2,000 mg/day) initially followed by maintenance doses (e.g., 250-500 mg/day). The most commonly prescribed antibiotic is tetracycline, but erythromycin and minocycline are also used. Such antibiotics, particularly at high doses can lead to side effects including gastrointestinal symptoms such as nausea, vomiting, abdominal pain, diarrhea, rashes, and other allergic reactions. Tetracyclines also can cause fetal harm if used during pregnancy.
Hormone therapy is another approach to treatment of acne based on the involvement of androgens in the development of acne. Estrogen therapy can be effective, but its usefulness is particularly limited in males by side effects such as gynecomastia, suppression of the testes, and uncertain effects on skeletal growth.
Isotretinoin (ACCUTANE) has been used in the treatment of severe nodulocystic acne. ACCUTANE therapy can lead to improvement in acne and can, in some cases exhibit the potential to prevent most permanent scarring from inflammatory acne. The severe side effects of ACCUTANE, however, are often prohibitive. Dry skin, dry eyes, headache, hair thinning, musculoskeltal pain, and other complications may result from treatment with ACCUTANE. Due to its teratogenicity, ACCUTANE should not be used by women who are pregnant or might become pregnant.
Thus, to date, there is typically a trade-off between efficacy and side effects, particularly in the treatment of more severe forms of acne. Accordingly, an effective treatment of acne, particularly its more severe forms, with clinically insignificant side effects is desired.